We have isolated and characterized a basic, heat-stable polypeptide growth factor from human serum that stimulates the replication of density inhibited Balb/c-3T3 cells, and density inhibited populations of diploid mouse or human fibroblasts. This highly purified polypeptide has a molecular weight of 1.3 x 10 to the 4th power daltons and isoelectric point of 9.7. Approximately 10 to the 11th power polypeptide molecules (8ng) in the growth medium allow the replication of 10 to the 4th power density inhibited cells. The polypeptide has been labeled with 125I and an antiserum has been produced in a rabbit allowing the development of a specific, highly sensitive radioimmunoassay. Approximately 50 ng of this polypeptide are present in 1 ml of whole human serum as judged by radioimmunoassay. The antiserum to the human polypeptide growth factor did not crossreact with growth factors in sera obtained from other species such as calf, guinea pig, rat and mouse. Studies on progress indicate that the human serum polypeptide growth factor derives largely from platelets. The growth factor is present in platelet-rich plasma but not in platelet-poor plasma as judged by both cell culture and radioimmunoassay. The growth factor polypeptide can be recovered from the platelets. The platelet polypeptide growth factor crossreacts with the antisera developed against the serum polypeptide. Its properties also appear to be similar to those of the cationic serum polypeptide. We propose its large scale isolation from outdated human platelets and the characterization of its chemical structure. The uptake and degradation of this polypeptide by normal and viral-transformed cells will be studied, and its presence in populations of human malignant cells grown in vitro will be quantitated by radioimmunoassay.